Soft ionization device and applications thereof

ABSTRACT

A soft ionization device is disclosed that comprises a series of electrodes having spacing less than the means free path of the molecules to be ionized. In some embodiments, the soft ionization device is used in various applications that require ion or electron sources such as biological or chemical reactors, ion milling, and numerous replacements for conventional hot cathode systems. In another embodiment, a valence spectrometer is disclosed that is configured to variably ionize molecules by their valiancy. In other embodiments, the ionization device is coupled to a spectrometer for the characterization of biological matter. Also disclosed is a preconditioner for preparing biological matter to be ionized.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit of U.S. Provisional ApplicationNo. 60/336,841 filed on Oct. 31, 2001, and U.S. Provisional ApplicationNo. 60/347,685 filed on Jan. 8, 2002, both of which are hereby fullyincorporated by reference.

BACKGROUND OF THE INVENTION

[0002] Ionization of gaseous molecules is conventionally initiated byphoton bombardment, charged particle impact, ultraviolet radioactiveionization, or by thermal electron beams. Such ionization techniques aretypically utilized for mass spectrometers and ion mobilityspectrometers. During ionization, depending on the level of impactenergy, one of two events occur, either electrons are ejected from atomsand molecules or the molecules themselves are fractured into complementof fragments with diverse charge states. These processes are known ashard ionization and while they can be utilized to provide a measurementindicative of the atoms and molecules contained within the ionizedsample, many components cannot be measured. Further, these ‘hard’ionization mechanisms are inefficient with approximately 0.1% of atomsor molecules ionized. In addition, conventional mass spectrometersrequire low pressure (“hard vacuum”) to operate to prevent highervelocity ions from colliding with a slower moving atoms and molecules(thermal velocities) that, during passage through the spectrometer,attenuate ion currents below detectable limits.

[0003] Moreover, conventional systems for ionization are susceptible toavalanche arcing when gases ionize in high electric fields. Thisphenomenon results because the mean free path length between molecules(at the relevant gas pressure) is greater than the electrode separationwithin the ionization device (empirical measurements showing thebreakdown voltage versus gas pressure are identified in the Paschencurve of FIG. 1). If conventional systems could be configured to operateunder the Paschen curve, then ionization would occur without avalanchearcing.

[0004] Current ionization systems coupled to detection systems areunable to characterize a wide range of biological matter. This is due inpart because most biological matter comprises complex molecularstructures that are susceptible to fracture, thus making it hard tocharacterize. In addition, some biological matter such as bacteria havevarying masses depending on the stage of replication. Accordingly, asconventional techniques necessarily fracture the biological matter,users are forced to examine a spectrum of mass data corresponding to thevarious atoms and molecules that made up the examined matter rather thanthe overall mass of the biological matter.

[0005] In addition, there are many applications that utilize an ion orelectron source that would benefit from a low cost efficient replacementsuch as field emission cathodes coated with low effective work-functionmaterials. However, such cathodes are difficult and costly tomanufacture and often have wide range of emissions and so there remainsa need for an improved electron source.

[0006] It will be appreciated that there are other applications that aredesirable for ionization including the characterization of ions by theirvaliancy, if an ionization system were sufficiently “soft”, efficient,small and inexpensive, and it is to this end that other aspects of theinvention are directed.

SUMMARY OF THE INVENTION

[0007] The invention is disclosed in a robust, efficient,temperature-insensitive, compact, and easy to manufacture ionizingdevice with a substrate having at least one opening. The substrateincludes a first conductive electrode on a first surface and a secondconductive electrode extending on a second surface that are separated byan insulating element to form an opening between the electrodes thewidth of the insulator. Preferably, the thickness of the insulatingelement is less than 1 micron. In some embodiments, the ionizing deviceis coupled to a detection system to characterize genetic material suchas deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins foruse in fields such as proteomics, drug discovery, diagnostics,identification of genetic material, metabolomics, and forensics. Inaddition, the detector elements within the detection system may beconfigured to collect detected genetic material so that they may laterbe blotted onto nitrocellulose paper.

[0008] In another embodiment, a system for producing ions and electronsis disclosed. This system includes an ionizing membrane having a thicksupporting portion with pores formed therein. Like the ionizing device,the membrane has first and second metal electrodes coated on surfaces ofthe thick supporting portion extending into the pores. The distancebetween the first and second metal electrodes within the pores of thethick supporting portion is less than the mean free path of a moleculebeing ionized so that molecules ionized by the pore will be subject tosecondary collision and thus fracture. A field generating element isalso used for directing the ions and electrons produced by the ionizingmembrane. The ions created by the system may be utilized for anyapplication requiring a source of ions such as ion focused milling,maskless ion implantation, ion beam lithography, semiconductor maskmodification, semiconductor chip wiring modifications, and ion massspectrometry, as well as the supply of pure species for chemicalreactors and biological reactors. Furthermore, as ions are produced,electrons are also “stripped” from the molecules which are directed bythe field generating element for use with applications such as dischargelight sources, flat panel displays, thyratrons, microwave switches,diodes, triodes, tetrodes, pentodes, and other replacements forhot-cathodes.

[0009] In another embodiment, a valence spectrometer is disclosed thatis configured to incrementally increase an ionization field so that allmolecules with a valence level equal or below the ionization fieldstrength will be ionized. Like the embodiments above, the systemincorporates an ionizing device as described above that is configured toionize molecules passing therethrough below a specific valence level. Adetection element coupled to said ionizing device determines the numberof ionized molecules.

[0010] Also disclosed is a system for ionizing multiple samples inparallel comprising an ionization membrane as described above with anarray of pores. Coupled to the ionization membrane are a plurality ofinlets configured to supply each sample to a single pore on the ionizingmembrane. In addition, each pore may have one or more detector elementsaligned thereto and configured to detect the passage of ions through thepores to a specified location (thereby providing measurements analogousto an ion mobility spectrometer). The current detected on the detectorelements is proportional to the concentration of matter on such elementsand can be used for quantitation measurements.

[0011] As many difficulties arise when ionizing a sample of biologicalmatter, a technique is disclosed (which may be used alone or incombination with an ion characterization system) for ultrasonicallyresonating a sample to remove materials that either confuse or are notinstructive for characterizing the constituents of the biologicalmatter. The technique utilizes a system includes a tubular memberconfigured to receive liquid samples having biological matter suspendedtherein. A piezoelectric generator is circumferentially coupled to thetubular member so that it may ultrasonically resonate the contents ofthe tubular member to remove undesirable matter. The resulting liquid isdelivered to a vaporizer that vaporizes the liquid prior to ionization.

[0012] Also disclosed are a soft ionization device and ioncharacterization system for the characterization of nuclear, biologicaland chemical threats as well as a technique for generating a unipolarplasma.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The features, objects, and advantages of the invention willbecome more apparent from the detailed description set forth below whentaken in conjunction with the drawings in which like referencecharacters identify correspondingly throughout and wherein:

[0014]FIG. 1 illustrates a Paschen curves for various gases;

[0015] FIGS. 2A-2B illustrates a soft ionization device of the presentsystem, with FIG. 2b showing a cross-section along the line 2B-2B inFIG. 2A;

[0016]FIG. 3 illustrates a cross section with details of the electricfields of the soft ionization device of FIGS. 2A-2B;

[0017]FIG. 4 illustrates an ion array mobility spectrometer utilizingthe soft ionization device of FIGS. 2A-2B;

[0018]FIG. 4 illustrates a valence spectrometer utilizing the softionization device of FIGS. 2A-2B;

[0019]FIG. 5 illustrates a cross section of a parallel ion mobilityspectrometer utilizing the soft ionization device 99 of FIGS. 2A-2Bwherein each pore has a separate lane of detectors correspondingthereto; and

[0020]FIG. 6 illustrates a preconditioner configured to pretreatbiological matter for ionization and characterization by a spectrometerutilizing the soft ionization device of FIGS. 2A-2B.

DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

[0021] With reference to the remaining figures, exemplary embodiments ofthe invention will now be described. The current invention is embodiedin a soft ionization device and various applications thereof. While theinvention is primarily detailed in connection with the severalembodiments herein, it will be appreciated by one of ordinary skill inthe art that the invention may be used for a variety of applicationswhere it is desirable to have an efficient ionization source as thecurrent invention provides a technique where the “mean free path”between molecules to be ionized is greater than electrode separation sothat only ionization occurs.

[0022] With reference to FIG. 1, a Paschen curve 100 for various gasesis illustrated. This curve represents the breakdown voltage of the gasesat various characteristic points. On the left side and under eachPaschen curve, generally in the area 101, ionization of the gas occursusing the special membrane described herein, to render the gases tooperate in this location.

[0023] The current invention provides a “soft” ionization technique isas it ionizes without fragmenting the molecular structure that is notsusceptible to temperature variations. This arrangement allows largeorganic compounds to be analyzed without breaking them into smalleratomic fragments.

[0024] Details of the membrane are illustrated in FIG. 2B, shows a crosssections of the membrane of FIG. 2A. The miniature soft ionizationdevice 99 is formed by micromachining one or more small pores 100(referred to herein as an array) through a relatively thin membrane 105.The membrane 105 may be, for example, of sub micron thickness. Thematerial 106 of the substrate itself may be silicon or any othereasy-to-machine material. Metal electrodes 120, 122 are located onrespective sides of the membrane 100. The metal can be any material suchas chrome or titanium or gold.

[0025] In formation of the soft ionziation device 99, a plurality ofpores such as 130 are formed from the bottom 132. The pores maygenerally taper as shown towards the top portion of the pore 133 (forexample, if the pore feature is generated using photolithography, eachpore may etched to form a pyramid-like shape with the sides of thepyramid projecting tapering at an angle of approximately 55°). The topportion of the pore 133 may have a dimension 136 which may be, forexample, 2 to 3 microns. An opening may be formed in the top metalcoating 120, with the same sized opening being formed in the bottommetal coating 122. For example, the pore may be formed by focusedion-beam milling (a maskless process).

[0026] The substrate material 106 also includes a dielectric layer 134.The thickness 136 of the dielectric layer sets the distance between themetal electrodes 120 and 122. The dielectric thickness can be to 200-300nm, and the dielectric can be for example, silicon nitride, alumina, orany other similar material. The important feature of the material is itsdielectric breakdown. The dielectric can in fact be thinner than 200 nm,in fact can be any thickness, with thicknesses of 50 nm being possible.

[0027] Preferably, the distance between the electrodes 120, 122 is lessthan 1 micron. When this small separation is maintained, electric fieldstrengths on the range of mega volts per meter are produced for eachvolt of potential difference between the electrodes 120, 122.

[0028] One of ordinary skill in the art will appreciate that membranesare preferably not formed simply from the thin, sub micron elements.Membranes that are formed in this manner are often too fragile tosustain a pressure difference across the membrane, or to survive a minormechanical shock. In the current embodiment, the thicker supportingsubstrate part 105 is used, and is back-etched through to the membrane.By forming the substrate in this manner with relatively thick substrateportions 105, 106, separated by back-etched pores 100, the structure ofthe device can be maintained with relatively small distance between theelectrodes.

[0029] In another embodiment the soft ionization device of the currentinvention is utilized to generate ions and electrons. As shown in FIG.3, neutral charged molecules 301 are ionized by electric fields(illustrated as 303) generated by the soft ionizing device 99. Electrons305 are stripped from the neutral charged molecules to form ions307—with the electrons and ions being dispersed according to theircharge. It will be appreciated that this arrangement may be used as anefficient source of electrons or ions. For example, this ion source maybe used for applications such as ion focused milling, maskless ionimplantation, ion beam lithography, semiconductor mask modification,semiconductor chip wiring modification, and ion mass spectrometry. Inaddition, the current soft ionization device may be utilized insituations where it is desirable to have a pure source of molecules, andso desired molecules may be dispersed by mass charge for supply to achemical or biological reactor. This embodiment may also be modified sothat the electric field diverts and directs electrons to a predeterminedlocation. Such an electron source can act as a replacement forconventional electron sources such as thermionic emission cathodes(hot-cathodes) treated with low-work-function materials. In particular,the soft ionization device may be used to generate electrons within avariety of gas discharge light sources (such as fluorescent bulbs),thyratrons, microwave switches, low pressure diodes, triodes, tetrodesor pentodes.

[0030] Another embodiment utilizes the ionization technique describedherein to form a valence spectrometer that may be used in connectionwith a mass spectrometer or other instrument unable to differentiatemolecules of similar mass/charge. The valence spectrometer incorporatesa soft ionization device that is configured to generate ionizationfields that can be incrementally increased over small intervals topermit differentiation of molecules having similar masses but withdifferent valence states (through an ion current measurement from aFaraday Cup placed adjacent to the soft ionization device or throughelectron current measurement from an anode placed adjacent to the softionization device). For example, the molecules CO and N have similarmasses but their valence states are 14.014 and 15.581 eV respectively.First, the user may choose to apply a field of 14.013 eV across the softionization device to ionize all molecules having a valence state of14.013 eV or less (as the spectrometer cannot differentiate what isdetected by the Faraday Cup). Next, the user would adjust the field to14.014 eV to determine the amount of CO in the sample. This process isthen repeated at the appropriate ionization field strengths (first at15.580 and second at 15.581) to determine the amount of N in the sample.As the valence spectrometer only requires a soft ionization device andeither a cathode (such as a Faraday Cup) or an anode, the size of thisdevice may be less than 1 mm by 1 mm.

[0031] Yet another use of the soft ionization device is to generate auni-polar (or primary ionized) plasma, provided that the field strengthacross the membrane is sufficiently high and the system is closed. Oncegenerated and after an initial start up period where the plasma willcollide with neutral molecules until they are swept out of the system,the plasma may be pumped by an accelerating electric (or magnetic) fieldand deflected by translational or rotational fields with the electronsbeing collected by a Faraday Cup. Unlike conventional systems thatoperate under millitorr level vacuum where molecules are still subjectto collision, the molecules within the unipolar plasma described hereininclude fewer slow moving (verses dominant proportion) neutral targetmolecules to collide with faster traveling ions nor does are there freeelectrons to neutralize ions (in fact, the unipolar ions repel eachother further reducing the likelihood of collision). In addition, asystem that generates unipolar plasma may also include a series ofdetection elements that are able to characterize the masses of allmolecules contained with the plasma to determine relativeconcentrations. Accordingly, unlike previous systems that suffer fromhard ionization effects and secondary ionization, the current systemprovides plasma substantially free of electrons or other differentiallyionized molecules.

[0032] One application of the soft ionization device is for use in aminiature ion mobility spectrometer 401 as shown in FIG. 4. Conventionalion mobility spectrometers use a shutter gate to provide short pulses ofions. The shortened pulses of ions are often limited to about 1 percentof the total number of ions that are available for detection. However,resolution of such a device is related to the width of the ion pulse.The width of the ion pulse cannot be increased without correspondinglydecreasing the resolution.

[0033] In the improved system of FIG. 4, total and continuous ionizationof sample gas and continuous introduction of all ions into the chamberis enabled. Sample gases are introduced as 400 into the soft ionizationdevice 405 of the type described above. In general, the soft ionizationdevice 405 could include either a single pore device or could havemultiple pores within the device.

[0034] Ions 410 from the membrane exit the membrane as an ion stream.Electrons in contrast move back behind (that is, to the other side of)the membrane, and further contribute to the ionization of the incominggases. The atoms or molecules are carried through the body of thespectrometer by a gas feed system 425. The gas feed system includeseither an upstream carrier gas supply and Venturi sampler, or adownstream peristaltic pump.

[0035] The ions are drawn towards the filter electrode 415 which receivealternating and/or swept DC electric fields, for the transversedispersal of the ions. A repetitive ramping of the DC fields sweepsthrough the spectrum of ion species.

[0036] An important feature of this ion mobility spectrometer 401 is thehigh field strengths that can be obtained. At moderate ionization fieldstrengths, for example <100,000 volts per meter, the mobility of ions atatmospheric and moderate pressures is constant. However, at higherionization field strengths, such as 2 million volts per meter orgreater, the mobility of the ions is nonlinear. The mobility changesdifferentially for high and low mobility ions. This change may be, forexample, by 20 percent. Therefore, by applying a waveform that is formedof a short high-voltage and a long low or negative voltage to the filterelectrodes, the ion species is disbursed between the filter electrodes.This waveform may be selected to provide a zero-time averaged field. Inoperation, the ions are transported laterally by a carrier gas stream. Alow strength DC field may be supplied in opposition to the other field.This fields applied to the filter electrode may straighten thetrajectory of specific ion species, allowing their passage through thefilter. The other ion species collide with the electrodes. Sweeping ofthe DC field may facilitate detection of the complete ion spectrum.

[0037] An array of detector electrodes 420 are located downstream of thefilter electrodes 415. The selected ions have straightened trajectories,and these filter electrodes deflect the straightened-trajectory ionsinto detection electrodes, where they are detected. The detected currentprovides a direct measure of the number of ions. The number of ions iseffectively proportional to the vapor concentration.

[0038] This system generally operates as conventional ion mobilityspectrometers but the soft ionization device (in connection with an ionmobility spectrometer and other types of spectrometers) allows for thesampling of the smallest possible ion masses (hydrogen having a mass ofone atomic mass unit) to large fragments with masses greater than 10,000AMU. For example, a soft ionization device in combination with an ioncharacterization system may characterize aqueous suspended proteins, RNAand ssDNA of around 500 kbases, and DNA of around 250 kbase-pairs aswell as biopolymers, sugar chains, and drug compounds (all of which arenot subject to fracture or decomposition using the soft ionizationtechniques disclosed herein) injected through a capillary nozzle into alow-pressure manifold where the suspended molecules, buffer complexesetc., are sublimated or vaporized into aerosol particles that aresubsequently ionized during passage through the soft ionization device.The MW range of instrument is greater than 10⁷ (compared with <10 forgel electrophoresis), which accommodates all proteins (>mega Daltoncapacity), RNA and ssDNA of around 500 kbases, and DNA of around 250kbase-pairs. In addition, the invention disclosed herein may beimplemented in parallel (as described in further detail below) such thatthousands of species are concurrently processed in minutes as an analogto gel electrophoresis (compared to one hundred per day with gelelectrophoresis and blotting), and are dispersed linearly with respectto mass and quantified with a resolution of better than 1 ng. Unlikeconventional systems, no a priori DNA snippets or antigens are requiredto identify molecules.

[0039] Forming the spectrometer in the manner described herein enablesthe system to be formed smaller, lighter, and with less cost than otherdevices of this type. This arrangement enables a wide range ofapplications; such as in situ biomedical sampling. One application isuse of the miniature mass spectrometer is for metabolomics (the study ofmetabolomes) measurements. As there are no electron beam filaments andthe like, any of the system components can operate at relatively higherpressures, for example pressures of 5 to 7 Torr or higher. With aFaraday Cup electrometer ion detector, sub-femtoamp levels ofsensitivity may be obtained. Moreover, the device can be made relativelysmall and low-power. For example a complete system may weigh 1 kg andconsume 10 watts. A sub-liter per second ion pump, or a membranemechanical pump, can provide sufficient vacuum pumping. This systemcould be used as a portable device for finding various characteristicsin exhaled breath, one technique for identifying metabolomes. Forexample, detection of carbon monoxide in exhaled breath may be used as ascreening diagnostic for diabetes or for other conditions which havemetabolic indicators

[0040] Another embodiment shown in FIG. 5, provides for a parallel ionmobility spectrometer 501 with a soft ionization device 505 having aplurality of linearly spaced pores 509. Each pore is positioned along alane comprised of an inlet 513 configured so that the sample input toeach pore is segregated from the other pores. Each pore, in parallel,ionizes the sample fed therethrough which is then accelerated by anaccelerator in the matter described above. A zero-time averagedispersive field deflects the ionized sample onto an array of detectorelectrodes 517 having a series of rows where the ion current of thedispersed ionized samples are measured. Preferably, the detectorelectrodes are metal plates of two-dimensional CCD or APS modifiedmatrix imagers.

[0041] The parallel ion mobility spectrometer may be used to performparallel analyses, including applications analogous to electrophoresis.If desired for applications such as proteomics, the samples that contactand discharge on the filter electrodes may be blotted ontonitrocellulose paper for subsequent uncontaminated species ‘cut-out’(via detector map). Alternatively, the spectrometer can dispersemolecules over a conductive (electrical) sheet, a substitute fornitrocellulose paper blots, on which traditional radiological probing orstaining could proceed. Furthermore, the spectrometer may incorporatemicro-channel plates having integrated electrodes such that various massmolecules may be directly deposited thereon and quantized based oncurrent. With these arrangements a spatial map is provided without therequirement tagging the desired samples with fluorescent, radioactive orother markers.

[0042] In yet another embodiment and as illustrated in FIG. 6, apreconditioner 601 is disclosed that may be used in connection withaspectrometer coupled to the soft ionization device disclosed above. Thepreconditioner provides a technique for pre-treating a sample toseparate desirable matter from undesirable matter (such as proteins,wall debris and polysaccharides, etc.) before characterization by themass spectrometer. The preconditioner comprises one or more tubes 605 inseries, preferably made from titanium, having an inner annulus 609.Circumferentially coupled to the outer surface of the tube are one ormore cylindrical piezoelectric generators 613 (rings) that generateultrasonic frequencies up to and including 1 MHz. The diameter of theannulus is approximately 1 mm or such other size to correspond with theaxial resonant cavity dimensions (for the aqueous suspended charge) ofthe piezoelectric generators.

[0043] In operation, the sample is suspended in a liquid such asdeionized water and passed through the annulus 609 of the tube 605. Thisprocess is repeated, if needed, until the desirable matter (such aswpore proteins, DNA, lipids, and carbohydrates of a bacterium (virus))is separated from the sample. This fluid is then vaporized in a lowpressure manifold from where it is drawn into the soft ionization deviceand for detection by an ion characterization system (i.e., massspectrometer, ion mobility spectrometer).

[0044] In some applications including anthrax detection, it is essentialto remove the undesirable background material. The sensitivity of theion characterization system must be sufficient to resolve theseinteractions and discriminate between the lowest concentration of BW andhighest background concentration of background Bioaerosols. For example,the edema protein of anthrax has a molecular size of 92,477 amu whilethe anthrax toxin lethal factor precursor has a molecular size of 93,785amu. In this range, the sampling system can distinguish molecular sizesas close as 10 amu. B. subtilis has a gyrA protein of 92,098 amu,difficult to distinguish by electrophoresis or chromatography, buteasily separated by the sampling system. In addition, depending on theconstituents of the sample, other pretreatment techniques, such asexposing the sample to warm deionized water (approximately 65° C.) maybe utilized prior to the preconditioner.

[0045] The exemplary embodiments have been primarily described withreference to figures illustrating pertinent components of theembodiments. It should be appreciated that not all components of acomplete implementation of a practical system are necessarilyillustrated or described in detail, nor are all of the varying componentlayout schema described. For example, the soft ionization device may beused for a variety of applications requiring precise characterization ofa large range of molecular weights such as a nuclear/chemical/biologicalagent detection system and for forensics. In addition, it will berecognized that the soft ionization device disclosed herein may be usedin connection with a wide variety of ion characterization systemsincluding: quadropole mass spectrometers, magnetic sector massspectrometer, and ion mobility spectrometers. Accordingly, only thosecomponents and architectures necessary for a thorough understanding ofthe invention have been illustrated and described in detail. Actualimplementations may contain more components or, depending upon theimplementation, fewer components. Modifications to the preferredembodiments will be apparent to those skilled in the art. Consequently,the scope of the present invention should not be limited by theparticular embodiments discussed above, but should be defined only bythe claims set forth below and equivalents thereof.

What is claimed is:
 1. A system, comprising: an ionizing device,comprising a substrate having at least one opening, a first conductiveelectrode extending on a first surface of the substrate and a secondconductive electrode extending on a second surface of the substrate, anda separator insulating element, having a thickness less than 1 micron,separating said first and second conductive electrodes at said at leastone opening, said first and second conductive electrodes being separatedby a width of said insulator; and a detection system coupled to saidionizing device for characterizing a genetic sample.
 2. The system ofclaim 1 wherein the genetic sample is chosen from the group comprisedof: deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins. 3.The system of claim 1 wherein the characterization of genetic materialis utilized for one of the applications selected from the groupcomprised of: proteomics, drug discovery, diagnostics, identification ofgenetic material, metabolomics, forensics.
 4. A system for producingions and electrons, comprising: an ionizing membrane having a thicksupporting portion with pores formed in the thick supporting portion andhaving first and second metal electrodes coated on surfaces of the thicksupporting portion extending into the pores in the thick supportingportion, where a distance between the first and second metal electrodeswithin the pores of the thick supporting portion is less than the meanfree path of a molecule being ionized; a field generating element fordirecting the ions and electrons produced by said ionizing membrane. 5.The system of claim 4, wherein the ions produced by the system are usedfor an application selected from the group comprised of: ion focusedmilling, maskless ion implantation, ion beam lithography, semiconductormask modification, semiconductor chip wiring modifications, ion massspectrometry, chemical reactors, biological reactors.
 6. The system ofclaim 4, wherein the electrons produced by the system are used for usedfor an application selected from the group comprised of: discharge lightsources, flat panel displays, thyratrons, microwave switches, diodes,triodes, tetrodes, pentodes, replacements for hot-cathodes.
 7. A system,comprising: an ionizing device, comprising a substrate having at leastone opening, a first conductive electrode extending on a first surfaceof the substrate and a second conductive electrode extending on a secondsurface of the substrate, and a separator insulating element, having athickness less than 1 micron, separating said first and secondconductive electrodes at said at least one opening, said first andsecond conductive electrodes being separated by a width of saidinsulator, wherein said ionizing device is configured to ionizemolecules passing therethrough below a specific valence level.
 8. Thesystem of claim 7 further comprising a detection element coupled to saidionizing device for determining the number of ionized molecules.
 9. Asystem for ionizing multiple samples in parallel comprising: an ionizingmembrane, comprising: a thick supporting portion with pores formed inthe thick supporting portion and having first and second metalelectrodes coated on surfaces of the thick supporting portion extendinginto the pores in the thick supporting portion, where a distance betweenthe first and second metal electrodes within the pores of the thicksupporting portion is less than the mean free path of a material beingionized; a plurality of inlets configured to supply each sample to asingle pore on said ionizing membrane.
 10. The system of claim 9,further including one or more detector elements for each pore configuredto detect the passage of ions to a specified location.
 11. The system ofclaim 10, wherein the sample is biological matter and the detectorelements are configured such that ions are neutralized and accumulatethereon and are later blotted on nitrocellulose paper forcharacterization.
 12. The system of claim 9, wherein the detectorelements quantitate the ions discharged thereon.
 13. The system of claim10, wherein each pore is coupled to an ion mobility spectrometer.
 14. Aspectrometer coupled to a soft ionization device for thecharacterization of nuclear, biological and chemical terrorist threats.15. A method for pretreating biological material for use with aspectrometer, wherein the improvement comprises, passing the biologicalmaterial through a tube having an ultrasonic generator coupled thereto.16. A system for use with an ionizer comprising: a tubular member,wherein said tubular member is configured to receive liquid sampleshaving organic material suspended therein; a piezoelectric generatorcoupled to said tubular member; wherein said generator is configured toultrasonically resonate said tubular member to treat the liquid; and avaporizer coupled to said tubular member and the ionizer; wherein saidvaporizer receives the treated liquid from said tubular member andvaporizes the treated liquid and delivers the liquid to the ionizer. 17.A system for ionizing molecules that is insensitive to temperature. 18.A system to ionize substantially all media passing therethrough togenerate a unipolar plasma.
 19. The system of claim 18 furthercomprising a series of detection elements configured to characterize themasses of all molecules contained with the plasma to determine relativeconcentrations.